Investigations for the common STIs, such as chlamydia, gonorrhoea, herpes, HIV, syphilis, and trichomoniasis, including culture, nucleic acid amplification tests (NAAT), and serology
Three testing modalities
- Three testing modalities, and the exam turns on choosing the right one
| Modality | Used for |
|---|---|
| NAAT | Chlamydia, gonorrhoea, M. genitalium, trichomonas, HSV, syphilis (lesion PCR) |
| Serology | HIV, syphilis, hepatitis B and C, HSV type-specific IgG (rarely useful) |
| Culture | Gonorrhoea - solely for antimicrobial susceptibility; not for diagnosis |
| Microscopy | Gram stain (urethral discharge), wet mount for trichomonas |
- Most STIs are asymptomatic -> testing is driven by risk, not symptoms
- *Test all exposed sites - pharyngeal and rectal infection is missed by a urine sample alone*
The standard Australian asymptomatic screen
- First-void urine (or self-collected vaginal swab) NAAT for chlamydia + gonorrhoea
- Throat and anorectal NAAT where exposure has occurred
- Serology: HIV, syphilis, hepatitis B (and hepatitis C if risk factors)
Epidemiology
- Chlamydia is the most notified STI in Australia - peak age 15-29
- Gonorrhoea and infectious syphilis have risen steeply over the last decade
- Syphilis outbreak among heterosexual populations and in remote Aboriginal and Torres Strait Islander communities -> congenital syphilis has re-emerged in Australia
- Therefore: syphilis serology in every antenatal woman (repeated in high-prevalence settings) and in any sexually active patient being screened
- Antimicrobial resistance is the defining pressure: ceftriaxone and azithromycin reduced susceptibility in gonorrhoea, macrolide resistance in >50% of M. genitalium
- Undiagnosed HIV in Australia is low (~9%) but late diagnosis remains common
Organism -> syndrome
| Organism | Presentation |
|---|---|
| Chlamydia trachomatis (D-K) | Usually asymptomatic; urethritis, cervicitis, PID, epididymo-orchitis, proctitis, reactive arthritis |
| C. trachomatis (L1-L3) | LGV - proctocolitis in MSM, inguinal buboes |
| Neisseria gonorrhoeae | Purulent urethritis, cervicitis, pharyngitis (usually asymptomatic), proctitis, disseminated gonococcal infection |
| Treponema pallidum | Primary chancre (painless) -> secondary rash incl. palms/soles -> latent -> tertiary |
| Mycoplasma genitalium | Non-gonococcal urethritis, persistent/recurrent urethritis, cervicitis, PID |
| Trichomonas vaginalis | Frothy discharge, vulvovaginal burning, "strawberry" cervix; often asymptomatic in men |
| HSV-1/2 | Painful vesicles/ulcers, dysuria, sacral radiculopathy |
| HIV | Seroconversion illness, then asymptomatic |
| HPV | Warts, cervical/anal dysplasia |
Window periods - the reason a negative test may be false
| Infection | Window |
|---|---|
| Chlamydia / gonorrhoea NAAT | ~2 weeks |
| HIV (4th generation Ag/Ab) | ~4-6 weeks; definitive at 3 months |
| Syphilis serology | ~4-6 weeks after exposure, up to 3 months |
| Hepatitis B | 6 weeks-6 months |
| Hepatitis C | RNA ~2 weeks; antibody 6-12 weeks |
- *A negative test inside the window does not exclude infection - always state when to retest*
Chlamydia and gonorrhoea
A. Chlamydia and gonorrhoea
- NAAT is the diagnostic test for both, from all exposed sites
- First-void urine (not mid-stream) in men; self-collected vaginal swab in women (equal or better sensitivity than an endocervical swab)
- Throat and rectal swabs where relevant - a large proportion of gonorrhoea is extragenital and asymptomatic
- Gonococcal culture in addition to NAAT, before treatment, from all infected sites - the only way to obtain susceptibilities
- Test of cure:
- Gonorrhoea: NAAT 2 weeks after treatment if no culture taken, resistance found, non-standard regimen, or pharyngeal infection
- Chlamydia: TOC only in pregnancy, rectal infection or suspected non-adherence
- Retest everyone at 3 months for reinfection (not test of cure - reinfection rates are high)
Syphilis - the algorithm
B. Syphilis - the algorithm
- Screen with a treponemal test (EIA/CMIA)
- Positive -> confirm with a second treponemal test (TPPA/TPHA) + a non-treponemal test (RPR) for titre
- Treponemal tests stay positive for life -> cannot distinguish active from treated infection
- RPR titre is the activity and treatment-response marker
- Four-fold (2 dilution) fall = adequate response; four-fold rise = reinfection or failure
- Dark-field microscopy or lesion PCR from a chancre - positive before serology converts
- LP for neurosyphilis if neurological/ophthalmic/otological signs, or treatment failure
- Prozone phenomenon: very high antibody in secondary syphilis can cause a false-negative undiluted RPR - ask the laboratory to dilute
HIV
C. HIV
- Fourth-generation antigen/antibody immunoassay - detects p24 antigen from ~2-3 weeks
- Reactive -> confirmatory testing + HIV RNA viral load, CD4, genotypic resistance
- Point-of-care rapid tests - useful for reach; a reactive result always needs laboratory confirmation
- Test at 4-6 weeks and again at 3 months after exposure
Mycoplasma genitalium
D. Mycoplasma genitalium
- NAAT, with macrolide resistance-mutation testing on the same specimen (23S rRNA mutations)
- >50% of Australian isolates are macrolide resistant -> resistance-guided therapy is standard
- *Do not screen asymptomatic people* - high carriage, no demonstrated benefit, drives resistance
- Test for it in persistent or recurrent non-gonococcal urethritis, cervicitis and PID
Trichomonas vaginalis
E. Trichomonas vaginalis
- NAAT is the test of choice (far more sensitive than microscopy)
- Wet-mount microscopy: motile flagellated organisms - specific, insensitive (~50-60%)
- Classic: frothy discharge, vulval burning, "strawberry cervix" (punctate cervical haemorrhages)
- High prevalence in remote Aboriginal and Torres Strait Islander communities; associated with preterm birth and increased HIV acquisition
Herpes simplex
F. Herpes simplex
- Swab the base of a deroofed vesicle/ulcer for PCR, with typing (HSV-1 vs HSV-2) - typing informs prognosis: HSV-2 recurs far more often
- *Type-specific serology is rarely useful* - cannot localise infection or date it; reserve for specific scenarios (e.g. a pregnant woman with a partner with known genital herpes)
Always offer alongside
G. Always offer alongside
- Hepatitis B serology (HBsAg, anti-HBc, anti-HBs) and vaccination if non-immune
- Hepatitis C antibody if injecting drug use, HIV-positive MSM, or other risk
- Cervical screening per the NCSP schedule (not part of an STI screen)
- Pregnancy test, contraception, PrEP discussion
Treatment - the numbers to know
Treatment follows the test, but empirical treatment is given where follow-up is uncertain.
Treatment - the numbers to know
| Infection | Treatment |
|---|---|
| Chlamydia (urogenital) | Doxycycline 100 mg bd x 7 days (azithromycin 1 g stat only if adherence is a concern) |
| Chlamydia (rectal, LGV) | Doxycycline 100 mg bd - 7 days rectal, 21 days for LGV |
| Gonorrhoea (genital/anorectal) | Ceftriaxone 500 mg IM stat (in 2 mL 1% lignocaine) PLUS azithromycin 1 g PO stat |
| Gonorrhoea (pharyngeal) | Ceftriaxone 500 mg IM PLUS azithromycin 2 g PO |
| Early syphilis (primary, secondary, early latent <2 yrs) | Benzathine penicillin G 1.8 g (2.4 million units) IM single dose |
| Late latent / unknown duration | Benzathine penicillin G 1.8 g IM weekly x 3 doses |
| Neurosyphilis | Benzylpenicillin IV 1.8-2.4 g 4-hourly for 15 days |
| M. genitalium | Resistance-guided: doxycycline 7 days, then azithromycin (macrolide-susceptible) or moxifloxacin 400 mg daily 7 days (macrolide-resistant) |
| Trichomonas | Metronidazole 2 g PO stat, or 400 mg bd x 7 days |
| Genital herpes (first episode) | Valaciclovir 500 mg bd x 5-10 days (or aciclovir/famciclovir) |
- Dual therapy for gonorrhoea is deliberate - azithromycin provides a pharmacological barrier to ceftriaxone resistance; ceftriaxone monotherapy only in specialist centres with culture surveillance
- Penicillin allergy in syphilis - penicillin is the only agent with proven efficacy in pregnancy and neurosyphilis: desensitise rather than substitute
- Jarisch-Herxheimer reaction - fever, myalgia, rash 6-12 h after treating syphilis; warn the patient; in pregnancy it can precipitate contractions and fetal distress
Alongside treatment - the part that is examined
- Partner notification and treatment - trace back 6 months for chlamydia/gonorrhoea, longer for syphilis by stage
- Tools: Let Them Know, Better to Know, contact tracing officers; patient-delivered partner therapy in some jurisdictions
- Abstinence for 7 days after treatment and until partners are treated
- Notification - chlamydia, gonorrhoea, syphilis, HIV, hepatitis B/C are notifiable in all Australian jurisdictions
- Retest at 3 months
- Offer PrEP, hepatitis B vaccination, HPV vaccination (to 25 free; available to 45)
- Screen for the others - an STI is a marker of risk, not an isolated event
- Pregnancy: syphilis serology at booking, repeat at 28 and 36 weeks and at delivery in high-prevalence settings; treat to prevent congenital syphilis
Co-infection and complications
- Co-infection is the rule - test for all when you find one
- HIV - ulcerative STIs (syphilis, HSV) increase both acquisition and transmission
- PID -> tubal infertility, ectopic pregnancy, chronic pelvic pain (chlamydia, gonorrhoea, M. genitalium)
- Disseminated gonococcal infection - migratory polyarthralgia, tenosynovitis, pustular rash
- Reactive arthritis - post-chlamydial, HLA-B27
- Fitz-Hugh-Curtis syndrome - perihepatitis
- Congenital syphilis, neonatal ophthalmia (gonococcal/chlamydial), neonatal herpes
- Trichomonas - preterm birth, low birth weight, increased HIV acquisition
- Antimicrobial resistance - gonococcal ceftriaxone/azithromycin, M. genitalium macrolide and fluoroquinolone
- Remote Aboriginal and Torres Strait Islander communities; men who have sex with men; sex workers; travellers; people who inject drugs
- Sexual assault; intimate partner violence; adolescent sexual health and consent
Natural history
- Most chlamydial and gonococcal infections are asymptomatic and many clear spontaneously - but the sequelae accrue silently
- PID in ~10-15% of untreated chlamydia; tubal factor infertility rises with each episode
- Syphilis stages
- Primary chancre 9-90 days, heals spontaneously in 3-6 weeks
- Secondary 6 weeks-6 months: rash including palms and soles, condylomata lata, mucous patches, alopecia; resolves untreated
- Latent - early (<2 yrs, infectious) and late
- Tertiary in ~1/3 untreated: gummata, cardiovascular (aortitis, aortic regurgitation, aneurysm), neurosyphilis (tabes dorsalis, general paresis, Argyll Robertson pupils)
- Neurosyphilis can occur at any stage, including early, particularly in HIV
- Genital herpes - lifelong latency in sacral ganglia; HSV-2 recurs ~4-5x/yr initially, declining over time; HSV-1 genital infection recurs rarely
- HIV - untreated, median ~10 years to AIDS; with modern ART, near-normal life expectancy and U=U
- Reinfection rates are high (10-20% at 3 months) - the reason for routine 3-month retesting rather than test of cure
- Congenital syphilis is preventable and its recurrence in Australia represents a systems failure, not a diagnostic one
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